Expression and function of transient receptor potential melastatin 3 in the spinal afferent innervation of the mouse colon

Am J Physiol Gastrointest Liver Physiol. 2023 Dec 12. doi: 10.1152/ajpgi.00230.2023. Online ahead of print.ABSTRACTAbdominal pain is a cardinal symptom of inflammatory bowel disease (IBD). Transient receptor potential (TRP) channels contribute to abdominal pain in preclinical models of IBD, and TRP melastatin 3 (TRPM3) has recently been implicated in inflammatory bladder and joint pain in rodents. We hypothesized that TRPM3 is involved in colonic sensation and is sensitized during colitis. We utilized immunohistochemistry, ratiometric Ca2+ imaging, and colonic afferent nerve recordings in mice to evaluate TRPM3 protein expression in colon-projecting dorsal root ganglion (DRG) neurons, as well as functional activity in DRG neurons and in colonic afferent nerves. Colitis was induced using dextran sulphate sodium (DSS) in drinking water. TRPM3 protein expression was observed in 76 % of colon-projecting DRG neurons, and was often co-localized with calcitonin gene-related peptide. The magnitudes of intracellular Ca2+ transients in DRG neurons in response to the TRPM3 agonists CIM-0216 and pregnenolone sulphate sodium were significantly greater in neurons from mice with colitis compared to controls. Additionally, the percentage of DRG neurons from mice with colitis that responded to CIM-0216 was significantly increased. CIM-0216 also increased the firing rate of colonic afferent nerves from control and mice with colitis. The TRPM3 inhibitor, isosakuranetin, inhibited the mechanosen...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - Category: Physiology Authors: Source Type: research